Pain and Chronic Kidney Disease

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1 Pain and Chronic Kidney Disease Frank Brennan Palliative Care Physician Department of Nephrology, St George Hospital Renal Supportive Care Symposium St George Hospital August

2 Epidemiology Effect on function and QOL Causes Management

3 Epidemiology of pain in CKD Dialysis patients 58 % Mean weighted prevalence over 36 studies Davison S, Koncicki H, Brennan F. Pain in Chronic Kidney Disease : A Scoping Review. Seminars in Dialysis 2014; 27(2):

4 49 % reported the pain as moderate to severe

5 Data on conservatively managed patients is more limited but shows similar prevalence and severity figures. Murtagh FEM et al. A Cross-sectional Survey of Symptom Prevalence in Stage 5 CKD managed without Dialysis. J Pall Med (2007) 10;6: Brennan FP. Et al. Symptoms in patients with CKD managed without dialysis. Progress in Palliative Care 2015 (in Press)

6 Impact on function and QOL

7 Data from 9 studies representing approximately 2100 HD patients found that pain was associated with lower HR- QOL. Table 2 in Davison S, Koncicki H, Brennan F. Pain in Chronic Kidney Disease : A Scoping Review. Seminars in Dialysis 2014; 27(2):

8 Impact on QOL Davison (2002) 69 dialysis patients 62% stated that pain interfered with their ability to participate and enjoy recreational activities.

9 51 % stated that pain caused them extreme suffering

10 41 % stated that pain caused them to consider ceasing Dialysis

11 Positive correlation with depression Davison S, Jhangri GS. J Pain Symptom Management 2005; 30(5):

12 Causes of Pain ESRD and its treatment Co-morbidities

13 1. Pain related to the disease: Polycystic Kidney Disease Renal Bone Disease Amyloid including Carpal Tunnel Syndrome Calciphylaxis

14 2. Pain secondary to treatment : PD pts with recurrent abdominal pain AV Fistulae > Steal syndrome Cramps Intradialytic headaches

15 3. Pain related to co-morbidities : OA Diabetic peripheral neuropathy PVD / IHD

16 Barriers to good pain management Patient related : Stoicism Not wanting to trouble the doctor Fatalism Fear of analgesic medications.

17 Clinician related : Inadequate education in pain management Lack of standardised management regimens across multiple pain syndromes Fatalism that pain is an unavoidable aspect of ageing and being on dialysis Seeing pain and symptoms generally are secondary priorities.

18 Opiophobia and opioignorance

19 Pain etiquette ENQUIRE REGULARLY RESPOND COMPASSIONATELY TREAT COMPETENTLY REFER WISELY

20 Principles of pain management 1. Always enquire about pain. 2. Treat the underlying cause of the pain. 3. Treat the pain meticulously. 4. Treat the pain proportionately. 5. Constantly reassess.

21 Pain management in patients with CKD

22 The traditional approach to the pharmacological management of pain has been to use the WHO Analgesic Ladder.

23 Certainly, the WHO Ladder has been validated in the context of ESKD and it remains a useful construct. Barakovsky AS et al. J Am Soc Nephrol 2006;

24 Could the WHO Analgesic Ladder be used as part of a broader perspective in pain management in the specific context of CKD?

25 Towards a strategic approach to pain management in patients with CKD

26 1. There are few studies examining pain management in the specific context of CKD

27 2. There are international evidence based guidelines and consensus statements on pain management of specific pain syndromes for the whole population.

28 Osteoarthritis Painful diabetic peripheral neuropathy Cancer pain

29 3. There is an increasing, although not complete, understanding of the pharmacology of analgesic medications in the context of CKD and their dialysability

30 These recommendations could be filtered through the known pharmacology of medications in the context CKD and their dialysability

31 Pain syndrome EB guidelines and consensus statements Evidence based Guidelines and Consensus Statements Pharmacokinetics/Pharmacodynamics P Pain management for patients in the context of CKD

32 A 69 y. o. man with Type II DM, diabetic nephropathy. ESKD HD for 4 years. Progressively more painful diabetic peripheral neuropathy

33 Evidence-based guideline : treatment of painful diabetic neuropathy. Report of the American Academy of Neurology et al. Bril V et al Neurology 2011; 76:

34 In painful diabetic neuropathy there is : Level A evidence Pregabalin Level B evidence for Gabapentin, Duloxetine, Amitriptline, Sodium Valproate, Morphine, Tramadol, Capsaicin, Isosorbide trinitrate spray and TENS

35 Gabapentinoids Gabapentin approx. 100 % renally excreted. Pregabalin % renally excreted.

36 H/Dialysis : Gabapentin dialysed Pregabalin dialysed (50 % in 4 hours)

37 PD Gabapentin possibly dialysed Pregabalin dialysed.

38 On Dialysis Pregabalin 25 mg after each Dialysis Titrate to effect

39 On conservative management egfr < 15 Pregabalin 25 mg every 2 nd night Titrate to effect

40 On conservative management egfr > 15 Pregabalin 25 mg nocte Titrate to effect

41 Davison S, Koncicki H, Brennan F. Pain in Chronic Kidney Disease : A Scoping Review. Seminars in Dialysis 2014; 27(2):

42 Koncicki H, Brennan F, Vinen K, Davison SN. An approach to pain management in End Stage Renal Disease Considerations for General Management. Seminars in Dialysis. April

43 The challenge of multiple pain aetiologies

44 A 73 year old woman Multiple co-morbidities including Type II DM, Diabetic Nephropathy on HD.

45 At first consultation : Osteoarthritis in lower back and knees bilaterally. Gouty arthropathy Carpal Tunnel syndrome Painful diabetic peripheral neuropathy (severe) Cramps on dialysis Post-operative pain

46 Role of Pain Services

47 Pharmacokinetics

48 Step 1 Paracetamol

49 Metabolised in liver 2-5 % excreted unchanged renally Inactive metabolites

50 HD dialysed PD not dialysed

51 No dose adjustment = 1g qid

52 It is considered the non-narcotic analgesic of choice for mild-moderate pain in CKD patients. Davison S, Ferro CJ. Management of Pain in CKD. Progress in Palliative Care 2009; 17:

53 Step 2 Tramadol

54 86% Metabolised in Liver Tramadol O- Desmethyl Tramadol N- Desmethyl Tramadol (M1) (Active) (Inactive)

55 90 % of Tramadol and its metabolites are renally excreted = 30 % unchanged; 60 % as metabolites.

56 Tramadol HD dialysed PD not known

57 Need for dose adjustment

58 Step 2 Tramadol is the least problematic of the Step 2 Analgesics for ESRD patients Nevertheless use with caution use a bd dose.

59 If on Conservative pathway egfr Commence 50mg bd Maximum 100mg bd

60 If on a Conservative pathway egfr < 15 or Dialysis Tramadol 50mg bd (maximum)

61 HD significantly removes Tramadol so dose best given post-dialysis

62 Codeine

63 Metabolised in Liver Codeine Morphine Norcodeine

64 Reports of : profound hypotension CNS and Respiratory depression

65 Not recommended in CKD. Davison S et al. Seminars in Dialysis 2014; 27(2):

66 Step 3 Morphine

67 Morphine Hepatic metabolism M-3-G M-6-G Kidneys

68 Morphine is not recommended in CKD

69 Step 3 Hydromorphone

70 Metabolised in Liver Hydromorphone Hydromorphone -3- Glucuronide

71 Hydromorphone HD H-3 G is dialysed PD not known

72 Much better tolerated than morphine with less toxic metabolites. Pharmacodynamic data shows less neuroexcitation compared to morphine no clinically significant opioid toxicity if given in low doses and monitored carefully. Davison S et al. Seminars in Dialysis 2014; 27(2):

73 Commence low ( mg) and qid. If tolerated q4hours Titrate up dose carefully once pain well controlled aim to convert to a safe long acting opioid. Davison S, Chambers EJ, Ferro CJ. Management of pain in Renal Failure. In Chambers EJ et al (eds) Supportive Care for the Renal Patient 2010, 2 nd ed, OUP.

74 Oxycodone

75 Oxycodone Short-acting Long-acting Endone Oxynorm Oxycontin

76 Metabolised by liver Active metabolites are eliminated mainly by hepatic metabolism. Less than 10 % excrete renally. Single dose study showed prolongation of oxycodone and its metabolites

77 Oxycodone HD dialysed PD not known

78 Overall consensus is that Oxycodone is reasonably safe to use in CKD if monitored carefully. Davison S et al. Seminars in Dialysis 2014; 27(2):

79 Fentanyl

80 Metabolised in Liver Inactive metabolites 5-10 % excreted unchanged renally Fentanyl is not dialysed (HD/PD)

81 Fentanyl is safe to use at standard doses - should monitor carefully. Davison S et al. Seminars in Dialysis 2014; 27(2):

82 Buprenorphine = Norspan

83 Buprenorphine Buprenorphine 3 Glucuronide (B-3-G) Norbuprenorphine (NorB) Both accumulate in CKD B-3-G is inactive ; NorB has minor analgesic quality

84 Buprenorphine HD dialysed PD dialysed

85 Buprenorphine may be given in standard doses to patients with CKD. Generally considered safe for use in CKD if monitored carefully. Davison S et al. Seminars in Dialysis 2014; 27(2):

86 Methadone

87 Metabolised in liver Excreted mainly in the feces. Some renal excretion of Methadone and its metabolites Not dialysed Safe to use, but requires skill in dosing regimen specialist use.

88 The hand that writes the opioid must also write the laxative

89 WHO Ladder ESRD summary Step Paracetamol 1g qid

90 Step Tramadol (adjusted dose)

91 Step 3 Hydromorphone Oxycodone Fentanyl Buprenorphine Methadone

92 The experience of the Renal Supportive Care Service, St George Hospital

93 Between March 2009 and July patients completed a POS (S) Renal at their first Renal Supportive Care clinic visit.

94

95 Of those 278 patients : 38% were dialysis patients 59% were conservatively managed patients (3% transplant and undecided)

96 Pain reported at first clinic visit - 62% of dialysis patients reported pain (51% moderate / overwhelming) - 56% of conservatively managed patients reported pain (51% moderate/ overwhelming)

97 Following those patients who had at least 3 clinic visits.

98 Between March 2009 and July 2015, 278 patients have completed a POS-S (Renal) at their first Renal Supportive Care clinic visit. 173 patients attended at least 3 visits (3 transplant patients were excluded from analysis)

99 Pain reported at third clinic visit

100 Pain Scores for Dialysis patients at first and third visits

101 Pain Scores for Conservative patients at first and third visits

102 Isolating those patients that reported severe to overwhelming pain at the first clinic visit. What happened to them by the 3 rd clinic visit?

103 Average Pain POS Scores for patients that scored Pain as severe or overwhelming at their first visit

104

105 What happened over time?

106 Pain Score- patterns - Dialysis patients - for patients with more than one visit - for patients that scored 3-4 for pain on their first visit (Severe to overwhelming) - for clinic visits where there were 5 or more patients

107 Pain Score- patterns - Conservative patients - for patients with more than one visit - for patients that scored 3-4 for pain on their first visit (Severe to overwhelming) - for clinic visits where there were 5 or more patients

108 Conclusion Pain is a common symptom in patients with CKD

109 Pain may be secondary to : The underlying renal disease Management of ESKD Co-morbidities

110 Requires a careful and calibrated approach based on : Identifying the aetiology of the pain Best evidence for management generally Pharmacokinetics of specific medications Where appropriate consider a non-pharmacological approach.

111 Role of Pain Services

112 Acknowledgements : Anna Hoffman for her preparation of the graphs. Elizabeth Josland, Alison Smyth, Gemma Collet, Mark Brown.

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